Tests will be performed to determine whether the vertebrate photoreceptor potential results exclusively from decreased Na ion influx. With the aid of infra-red, microscopic observation, intracellular recordings will be made from single photoreceptors in the isolated retina. Extracellular ionic composition will be altered by using a recently developed perfusion technique. The ionic basis for potential generation in horizontal cells and bipolar cells will then be studied using this technique. It has been proposed that the decreased Na ion influx which presumably generates the receptor potential is mediated by light-induced release of Ca ions otherwise bound to rod disks. To test this hypothesis, receptor potentials and resting membrane potential will be recorded while intracellular free (Ca ions) is altered. This will be accomplished by iontophoresis of EGTA, a Ca ions-chelating agent, from the electrode. Bipolar cells are thought to receive information (1) by direct signaling from receptors (for central stimuli), and (2) via horizontal cells (for peripheral stimuli). However, it is not known whether the horizontal cell acts directly on the bipolar membrane or indirectly upon receptors. Direct horizontal to bipolar connections will be sought by injecting current into a horizontal cell while membrane potential and response to light of a bipolar cell are recorded. Feedback from horizontal cells to receptor cells has been identified, but is very sensitive to hypoxia and surgical trauma. To ascertain the strength of the feedback in vivo, recordings will be made from receptor cells in an alive anesthetized animal. Psychophysical experiments using human rod monochromats have enabled the rod system to be studied in isolation, without contamination from cone signals. In the hope of obtaining animals with simplified retinal circuitry, existing mouse mutants will be screened for visual dysfunction, using the electroretinogram (ERG). Perhaps this will also reveal modified mammalian retinas which serve as models of human disease.